The objective of this research is to arrive at a detailed understanding of the catalytic mecanism of the enzyme DNA ligase by synthesizing severa DPN analogues which have had their adenylyl phosphorus atoms deactivated to nucleophilic attack by the substitution of an adjacent oxygen atom by an element or group which is less electronegative. The substituted elements or groups will be nitrogen, esterified and non-esterified sulfur, and a methylene group. The use of these DPN analogues with enzyne should allow unambiguous demonstration of whether the covalent ligase-AMP complex is a true intermediate in the reaction or reversibly formed side product. In addition, the effect of cordycepin triphosphate (3'-deoxyadenosine triphosphate) upon DNA synthesis in E. coli cells rendered permeable to nucleoside triphosphates by treatment with toluene is being examined.